Proton acceleration by irradiation of isolated spheres with an intense laser pulse

We report on experiments irradiating isolated plastic spheres with a peak laser intensity of 2-3 x 10(20) W cm(-2). With a laser focal spot size of 10 mu m full width half maximum (FWHM) the sphere diameter was varied between 520 nm and 19.3 mu m. Maximum proton energies of similar to 25 MeV are achieved for targets matching the focal spot size of 10 mu m in diameter or being slightly smaller. For smaller spheres the kinetic energy distributions of protons become nonmonotonic, indicating a change in the accelerating mechanism from ambipolar expansion towards a regime dominated by effects caused by Coulomb repulsion of ions. The energy conversion efficiency from laser energy to proton kinetic energy is optimized when the target diameter matches the laser focal spot size with efficiencies reaching the percent level. The change of proton acceleration efficiency with target size can be attributed to the reduced cross-sectional overlap of subfocus targets with the laser. Reported experimental observations are in line with 3D3V particle in cell simulations. They make use of well-defined targets and point out pathways for future applications and experiments.DFG via the Cluster of Excellence Munich-Centre for Advanced Photonics (MAP) Transregio SFB TR18NNSA DE-NA0002008Super-MUC pr48meIvo CermakCGC Instruments in design and realization of the Paul trap systemIMPRS-APSLMUexcellent Junior Research FundDAAD|ToIFEEuropean Union's Horizon research and innovation programme 633053Physic

Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1

The treatment of Human African Trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important and pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp. has been identified as a candidate target and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from T. brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. 8 compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development

Industrial work placement in higher education: a study of civil engineering student engagement

For civil engineering undergraduates, the opportunity to spend a period of time in formal industrial work placement provides an invaluable learning experience. This paper reviews student engagement with short-term industrial placement and provides analysis of questionnaires (n=174) returned by undergraduates studying civil engineering at four Higher Education Institutes (HEI’s) in the West of Scotland. The data captures industrial placement statistics, employability skill-sets and presents brief testimonies from students. Whilst the journey to becoming a professional civil engineer is undoubtedly enhanced by short-term placement clear opportunities exist for HEI’s to affect and change existing pedagogical discourse. Commentary is likely to resonate beyond civil engineering and serve as a timely reminder of the need to re-invigorate academia / industry curriculum partnerships

Reactivity worth of control rods in the beryllium oxide moderated pebble bed reactor.

Preliminary and final studies are reported for the worth of tubular control rods in a beryllium oxide moderated pebble bed reactor system. In the preliminary study the consideration of ball flow forces the investigation of a number of control rod arrangements. In addition, a range of rod sizes is considered. In the final study a particular rod size and pattern is chosen for more detailed investigation. For the intermediate reactor cores under consideration the control rods must absorb appreciably in the KeV region. A feature of the final study is the accurate way the epithermal absorption can be taken into account while using a three group model in the reflected reactor. The preliminary study is not so accurate but is useful for comparative purposes

Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors

N-Myristoyltransferase (NMT) represents a promising drug target for human African trypanosomiasis (HAT), which is caused by the parasitic protozoa Trypanosoma brucei. We report the optimization of a high throughput screening hit (1) to give a lead molecule DDD85646 (63), which has potent activity against the enzyme (IC50 = 2 nM) and T. brucei (EC50 = 2 nM) in culture. The compound has good oral pharmacokinetics and cures rodent models of peripheral HAT infection. This compound provides an excellent tool for validation of T. brucei NMT as a drug target for HAT as well as a valuable lead for further optimization.</p

<i>Trypanosoma brucei</i> DHRF-TS revisited:characterisation of a bifunctional and highly unstable recombinant dihydrofolate reductase-thymidylate synthase

<div><p>Bifunctional dihydrofolate reductase–thymidylate synthase (DHFR-TS) is a chemically and genetically validated target in African trypanosomes, causative agents of sleeping sickness in humans and nagana in cattle. Here we report the kinetic properties and sensitivity of recombinant enzyme to a range of lipophilic and classical antifolate drugs. The purified recombinant enzyme, expressed as a fusion protein with elongation factor Ts (Tsf) in ThyA^- <i>Escherichia coli</i>, retains DHFR activity, but lacks any TS activity. TS activity was found to be extremely unstable (half-life of 28 s) following desalting of clarified bacterial lysates to remove small molecules. Stability could be improved 700-fold by inclusion of dUMP, but not by other pyrimidine or purine (deoxy)-nucleosides or nucleotides. Inclusion of dUMP during purification proved insufficient to prevent inactivation during the purification procedure. Methotrexate and trimetrexate were the most potent inhibitors of DHFR (<i>K</i>_i 0.1 and 0.6 nM, respectively) and FdUMP and nolatrexed of TS (<i>K</i>_i 14 and 39 nM, respectively). All inhibitors showed a marked drop-off in potency of 100- to 1,000-fold against trypanosomes grown in low folate medium lacking thymidine. The most potent inhibitors possessed a terminal glutamate moiety suggesting that transport or subsequent retention by polyglutamylation was important for biological activity. Supplementation of culture medium with folate markedly antagonised the potency of these folate-like inhibitors, as did thymidine in the case of the TS inhibitors raltitrexed and pemetrexed.</p></div

Review: The increasing importance of carbon nanotubes and nanostructured conducting polymers in biosensors

The growing need for analytical devices requiring smaller sample volumes, decreased power consumption and improved performance have been driving forces behind the rapid growth in nanomaterials research. Due to their dimensions, nanostructured materials display unique properties not traditionally observed in bulk materials. Characteristics such as increased surface area along with enhanced electrical/optical properties make them suitable for numerous applications such as nanoelectronics, photovoltaics and chemical/biological sensing. In this review we examine the potential that exists to use nanostructured materials for biosensor devices. By incorporating nanomaterials, it is possible to achieve enhanced sensitivity, improved response time and smaller size. Here we report some of the success that has been achieved in this area. Many nanoparticle and nanofibre geometries are particularly relevant, but in this paper we specifically focus on organic nanostructures, reviewing conducting polymer nanostructures and carbon nanotubes

Breaking barriers: female and Hispanic undergraduate students experience gains in self-confidence and tolerance for obstacles during a sustainability-centered internship program in the USA

Previous research has shown that female and Hispanic students who are underrepresented in science, technology, engineering and mathematics (STEM) face more educational barriers than their non-Hispanic, male peers. However, little research has been conducted on the effects of intersectional identities in the STEM space. In an effort to bridge the gap in underrepresented students\u27 experience, the PSEG Institute for Sustainability Studies organizes a paid, interdisciplinary, team-based, experiential learning and internship program called the Green Teams that occurs during 10 weeks of the summer. The Green Teams Program strives to provide undergraduate students from all backgrounds–academically, economically, and demographically–an opportunity to develop their abilities in STEM fields and prepare them to enter the professional world. Based upon a survey given post-internship, self-reported learning gains for all students were analyzed to determine if the program had a significantly greater impact on students who are from groups traditionally underrepresented in STEM in their STEM-related learning gains and their confidence in STEM disciplines. Through t-tests, a Principal Component Analysis (PCA), and a 2-way factorial Analysis of Variance (ANOVA), Hispanic and female participants were found to report significantly higher learning gains than their counterparts in multiple STEM areas from increased tolerance for obstacles to gains in self confidence. The results of the study suggest Hispanic and female students benefit from paid work experiences in STEM with diverse peers and intentional, supportive mentoring. This research on the Green Teams Program provides insight into how this approach positively impacts STEM education of individuals from traditionally underrepresented groups in STEM. The findings may help to further guide the development of the Green Teams Program and the adoption of paid, interdisciplinary, team-based, experiential learning and internship experiences in additional academic STEM settings